Whether care giving has adverse effects on the caregiver's physical and cognitive functioning remains uncertain due to inconsistent research findings and methodological limitations that include: assessment of caregiver status at baseline only - not incorporating changes in caregiver status over the follow up period; evaluation of health outcomes at a single follow up time; and absence of measures of perceived stress and biological markers that would allow direct tests of bio-psychosocial models of care giving-related stress and health decline. The proposed study is a competitive renewal of Caregiver-SOF, which is an ancillary study to the Study of Osteoporotic Fractures (SOF), a multi-site study of the risk of fractures and falls in elderly women. The Caregiver-SOF sample has 1069 SOF participants (mean age=81 years) who were informal caregivers (n=375) and non-caregivers (n=694) matched on SOF site, age, race, and zip code. They have had three annual home-based interviews that included standardized questions on the care-giving situation and caregiver status transitions, perceived stress, depressive symptoms, and self-reported ADLs and lADLs; performance-based measures of physical functioning (timed walk, grip strength, chair stands); cognitive tests of speed/attention (Digit Substitution Test) and verbal memory (Hopkins Verbal Learning Test); and measured weight. This proposed study will add two home-based interviews with 734 surviving Caregiver-SOF participants. Trained SOF interviewers will re-administer the questionnaires and physical and cognitive measures that have been administered previously, for a total of five assessment points. These data will be linked to SOF data on mortality and lnterleukin-6 (IL-6) using stored serum from a concurrent SOF exam at two SOF sites. Hypotheses will be tested that 1) compare caregivers and non-caregivers, and transitions in caregiver status, on change in physical (namely, self-reported and performance-based functional status, weight change, and mortality) and cognitive health status using repeated measures and Cox proportional hazards modeling; 2) examine the role of IL-6 as a mediator in the pathway from care-giving and chronic stress to physical and cognitive health decline; 3) evaluate methodologic reasons for higher rates of health decline in spouse caregivers that have been observed in recent studies; and 4) use growth curve modeling to analyze trajectories of change in stress and health outcomes. This study will replicate and extend the results of previous studies by providing insight into etiologic, biological, and methodological factors in the associations of care-giving stress with physical and cognitive health outcomes. Study results will guide interventions to reduce effects of stress on physical and cognitive health in older caregivers, and older adults in general.